Extrahepatic metabolism of sevoflurane in children undergoing orthotopic liver transplantation

Background: Sevoflurane is metabolized by cytochrome P450 and produces inor ganic fluoride. The anhepatic phase of liver transplantation provides a use ful tool to study the extrahepatic metabolism of drugs. The authors therefo re studied the extrahepatic metabolism of sevoflurane by measuring the fluo ride production in children receiving sevoflurane solely during the anhepat ic phase of orthotopic liver transplantation. Methods Children with end-stage liver disease undergoing orthotopic liver t ransplantation were studied. Anesthesia was provides with isoflurane, sufen tanil, and pancuronium, In one group, isoflurane was replaced by sevofluran e as soon as the liver was removed from the patient and maintained until re perfusion of the new liver. Arterial blood samples were drawn at induction, before removal of the liver, 15 min and 30 min after the beginning of the anhepatic phase, at the unclamping of the new Liver, and finally 60 and 120 min after the unclamping, Plasma fluoride concentrations were determined b y ion-selective electrode, Results: No differences between the two groups (n = 10) regarding age, weig ht, duration of the anhepatic phase, or basal level of inorganic fluoride w ere found. The fluoride concentration increased significantly as soon as se voflurane was introduced; it remained stable in the group receiving isoflur ane, The peak fluoride concentration was also significantly higher in the f irst group (mean +/- SD: 5.5 +/- 0.8 mu M (sevoflurane group) versus 1.4 +/ - 0.5 mu M (isoflurane group) P < 0.05), Conclusions: These results demonstrate the existence of an extrahepatic met abolism of sevoflurane at least in children with end-stage liver disease.